The field of the invention is positron emission tomography (PET) scanners, and particularly the quantification of tissue metabolic activity.
Positrons are positively charged electrons which are emitted by radionuclides that have been prepared using a cyclotron or other device. The radionuclides most often employed in diagnostic imaging are fluorine-18 (18F), carbon-11 (11C), nitrogen-13 (13N), and oxygen-15 (15O). These are employed as radioactive tracers called “radiopharmaceuticals” by incorporating them into substances, such as glucose or carbon dioxide. The radiopharmaceuticals are injected in the patient and become involved in such processes as blood flow, fatty acid and glucose metabolism, and protein synthesis.
As the radionuclides decay, they emit positrons. The positrons travel a very short distance before they encounter an electron, and when this occurs, they are annihilated and converted into two photons, or gamma rays. This annihilation event is characterized by two features which are pertinent to PET scanners—each gamma ray has an energy of 511 keV and the two gamma rays are directed in nearly opposite directions. An image is created by determining the number of such annihilation events at each location within the scanner's field of view.
Positron-emission tomography (PET) imaging of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) is increasingly used to assess metabolic activity of pulmonary inflammatory cells. The uptake rate of 18F-FDG by tissue can be computed either by compartmental modeling or by a graphical technique. A prerequisite for either analysis is the knowledge of the input function to the system in the form of a plasma time-activity curve. Acquisition of such an input function typically involves sequential blood sampling, a process that is invasive, is prone to measurement artifacts, involves radiation and blood exposure to clinical staff, and adds costly laboratory procedures.
To avoid, or minimize, manual blood sampling, substantial effort has been devoted to developing alternative techniques that have been successfully applied to estimate 18F-FDG uptake in tumors and brain. Some of these known techniques involve population-based assumptions about the input function morphology, while others directly estimate the input function from blood pool regions of interest (ROI) in the PET images.
Analysis of 18F-FDG uptake by inflamed non-neoplastic lung presents particular challenges which render prior methods unsatisfactory. Population-based assumptions required by prior methods are not available and may vary for different types of pulmonary inflammation. Also, estimates of the input function from blood pool ROI's are affected by partial volume effects, and by activity spillover from the heart or inflamed pulmonary tissues. Moreover, in contrast to brain, heart or solid tumor tissues, where the blood-to-tissue fraction is low, in lung parenchyma blood volume may account for as much as half of the parenchymal volume. As a result, the blood compartment is a dominant source of lung 18F-FDG activity, and particularly during the early phase following tracer injection. Because early phase kinetics affects estimates of distribution volumes and rapid rate constants, accurate assessment of the early phase input function might be crucial for characterizing the inflamed lung. Although techniques to reduce blood sampling are available, they seem to have limited accuracy in describing the early phase input function, or are unable to assess the early phase of the input function. Current techniques involving image-derived assessment of the early input function either neglect partial volume effects and activity spillover artifacts, or they mathematically correct for these artifacts using measured or approximated anatomic dimensions of the blood pool ROI used.